Cesium carbonate → 5-(4-Ethoxy-3-methoxy-2-(methoxymethoxy)phenyl)isobenzofuran-1(3H)-one

HRID 2171131Notes

Reaction equation

HRID 2171131 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH3:10])=[C:4]([O:11][CH3:12])[C:3]=1[O:13][CH2:14][O:15][CH3:16].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:31]2[CH:32]=[C:33]3[C:37](=[CH:38][CH:39]=2)[C:36](=[O:40])[O:35][CH2:34]3)O1>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:9]([O:8][C:5]1[CH:6]=[CH:7][C:2]([C:31]2[CH:32]=[C:33]3[C:37](=[CH:38][CH:39]=2)[C:36](=[O:40])[O:35][CH2:34]3)=[C:3]([O:13][CH2:14][O:15][CH3:16])[C:4]=1[O:11][CH3:12])[CH3:10]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 580746235-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-2-benzofuran-1-oneHCID 674628591-Bromo-4-ethoxy-3-methoxy-2-(methoxymethoxy)benzene

Product 1

HCID 674628925-(4-Ethoxy-3-methoxy-2-(methoxymethoxy)phenyl)isobenzofuran-1(3H)-oneYield 40.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A stirring solution of 1-bromo-4-ethoxy-3-methoxy-2-(methoxymethoxy)benzene (200 mg, 0.722 mmol) in dimethylformamide (5 mL) was purged with argon for 1 h, to this cesium carbonate (700 mg, 2.166 mmol), Pd(PPh3)4 (41 mg, 0.036 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isobenzofuran-1(3H)-one (280 mg, 1.08 mmol) were added and the resultant reaction mixture was heated to 80-90° C. for 3 h. The reaction mixture was cooled to RT, filtered and the filtrate was diluted with water and extracted with ethyl acetate (3×). The combined ethyl acetate layers were washed with brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure. Purification of the residue by column chromatography (silica gel, 0-20% ethyl acetate in pet ether) afforded 5-(4-Ethoxy-3-methoxy-2-(methoxymethoxy)phenyl)isobenzofuran-1(3H)-one as a solid (100 mg, 40%).

Workup

  1. additionwere added
  2. customthe resultant reaction mixture
  3. temperatureThe reaction mixture was cooled to RT
  4. filtrationfiltered
  5. additionthe filtrate was diluted with water
  6. extractionextracted with ethyl acetate (3×)
  7. washThe combined ethyl acetate layers were washed with brine
  8. dry with materialdried over anhydrous sodium sulphate
  9. concentrationconcentrated under reduced pressure
  10. customPurification of the residue by column chromatography (silica gel, 0-20% ethyl acetate in pet ether)

Sources & evidence

ORD record
ord-9230f57ccd8c45f7a1289c1c258dd24f
Source dataset
uspto-grants-2015_06
Patent number
US09051290B2

Reaction notes

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